Research Interests

hematopoiesis, leukemia

Biography

Dr. Friedman is the King Fahd Professor of Oncology and Professor of Pediatrics at the Johns Hopkins University School of Medicine. He received his M.D. from the Harvard Medical School (1983), did his Pediatric internship and residency and Boston Children's Hospital (1983-86), and completed a fellowship in Pediatric Hematology-Oncology at Johns Hopkins (1986-89). As a fellow he did post-doctoral research at the Carnegie Institution Department of Embryology located on the Johns Hopkins Homewood campus. Dr. Friedman has served on the Pediatric Oncology faculty at Johns Hopkins since 1989. His laboratory focuses on investigation of normal and abnormal blood-cell formation. Dr. Friedman also cares for children with cancer, specializing in the treatment of leukemia.

Certifications

Research Summary

RUNX1 is a transcription factor required for the formation of the hematopoietic stem cell (HSC) and for its further maturation. RUNX1 is commonly mutated or involved in chromosomal translocations associated with AML or ALL. Dr. Friedman''s laboratory is investigating the mechanisms that allow RUNX1 to regulate normal hematopoietic stem cells and myeloid differentiation and to stimulate cell cycle progression. He ultimately envisions developing means to manipulate RUNX1 to assist formation and expansion of HSC from embryonic stem cells and to assist formation of autologous neutrophils to benefit patients with neutropenia. In addition, Dr. Friedman is investigating how mutations of RUNX1 or its partner CBFb contribute to acute leukemia, focusing on CBFb-SMMHC, a fusion oncoprotein expressed from the inv(16) chromosome in a subset of AML patients. Ultimately, he would like to identify small molecules that target CBFb-SMMHC to assist in the therapy of AML.

C/EBPa is a transcription factor required for formation of normal neutrophils and monocytes. C/EBPa is also commonly mutated in blasts derived from patients with AML. Dr. Friedman''s laboratory is investigating how C/EBPa cooperates with other proteins, including cytokines such as G-CSF or M-CSF, to control normal myeloid development. In addition, he is investigating how mutant forms of C/EBPa contribute to AML, in particular focusing on how interaction between C/EBPa and another transcription factor, NF-kB, inhibits apoptosis. By mapping the amino acids through which these proteins interact, Dr. Friedman hopes to ultimately design small molecules that prevent their interaction to induce leukemic cell death and contribute to the therapy of AML. As C/EBPs and NF-kB are also expressed also in other malignancies and in inflammatory cells which contribute to cancer formation and progression, such a small molecule might in addition have broader utility as a novel therapeutic.

Lab:

Dr. Friedman investigates mechanisms through which normal proteins control the formation of bone marrow stem cells and how these stem cells then develop into neutrophils and monocytes. He is also studying how normal bone marrow cells become transformed into acute myeloid leukemia (AML). In conducting these studies he focuses on two proteins, RUNX1 and C/EBPa, which regulate normal bone marrow development but are also commonly mutated in AML. Dr. Friedman is attempting to build on his basic research to develop useful clinical applications. In particular, he is pursuing small molecules that interfere with the action of leukemic RUNX1 or C/EBPa proteins as potential novel therapies for AML, and he is investigating means to expand normal blood stem cells to benefit patients with marrow failure or those many patients receiving chemotherapy who would benefit from blood product support to avoid anemia, bleeding, and infections.